系统性红斑狼疮遗传方式的分析

为探讨系统性红斑狼疮（ＳＬＥ）的遗传方式，对２２０例ＳＬＥ家系资料作了分析。结果６．８％的患者有红斑狼疮家族史，分离比为０．０２１３７，不符合单基因遗传；遗传度为５７％±７．５％。患者出生顺序在第５胎次以上较多并接近显著，提示ＳＬＥ的发病可能与遗传和环境有关。用Ａ类回归Ｌｏｇｉｓｔｉｃ模型进行复合分离分析，结果拒绝单纯环境模型、显性模型和无传递模型，接受主基因模型、隐性模型和共显性模型。提示单纯环境不能完全解释ＳＬＥ的发病，ＳＬＥ存在上下代的传递，可能有多主基因效应，这些主基因可能为隐性和／或共显性遗传。另外，劳累、病毒感染、日晒、寒冷刺激等可能是发病的诱因。以上均提示ＳＬＥ是一种多因子遗传病。     

原发性高血压病遗传学研究

对５０例有家族史的遗性高血压患者进行家系、遗传度的调查及ＨＬＡ单倍型的关联分析，并以２１例无家族史的非遗传高血压及１００例正常无关人对照，结果发现：（１）遗传性高血压以多基因遗传为主，遗传度的加权平均值为５９．７２±８．１２％；（２）遗传性高血压与ＨＬＡ－Ｂ７５，ＤＲ１，ＤＱ７显著相关，Ｂ７５－ＤＱ７是连锁不平衡，非遗传传高血压ＨＬＡ－Ｂ８抗原偏高，提示原发性高血压具有遗传基础，ＨＬＡ基因可能存在     

婴幼儿哮喘的遗传流行病学调查和分析

目的探讨遗传因素在婴幼儿哮喘患病中的作用。方法采用遗传流行病学调查方法,对婴幼儿哮喘先证者(102例)的一、二级亲属进行患病率(q)、危险因素比数比(OR)、遗传度(h2)及二项分布拟合计算。结果先证者一、二级亲属哮喘及过敏性疾病q显著高于对照组(P<0.05,<0.001);用二项分布拟合分析其家族中哮喘患者分布均超过二项分布的概率范围;一、二级亲属哮喘h2分别为86.50±8.79%,68.80±11.97%,其加权平均为80.30±2.25%,一级亲属经吸烟分层分析,重度吸烟组q和h2为最高。结论婴幼儿哮喘有明显家族聚集性,遗传因素起主要作用,符合多基因遗传病,环境因素起协同作用。     

系统性红斑狼疮的复合分离分析

目的 对中国南方地区300例系统性红斑狼疮患者家系的遗传方式进行研究,探讨可能的遗传模式。方法 用遗传流行病统计分析Logistic模型截尾性状分离分析（statistical analysis for genetic epidemiolgy-REGTL,SAGE-REGTL）软件进行复合分离分析,探讨可能的遗传模式和致病基因频率。结果 SAGE－REGTL软件分析显示存在主基因效应、加性模型拟合最好,支持在多基因基础上有符合孟德尔遗传的主基因效应,基因频率为0．336,随年龄的增加,遗传因素所起作用减小,环境因素增加。结论 系统性红斑狼疮为加性遗传模型,基因频率为0．336。     

系统性红斑狼疮多因子遗传的通径分析

本文应用ATRIBUTE软件对215例先证者及其核心家系进行了通径分析,以探讨SLE可能的遗传模式。结果表明,与一般模型比较,H＝0和（H＝0,C＝0）的假设被拒绝,提示SLE不符合单基因遗传,存在多基因遗传模式。本病可能是一多因子疾病,遗传度为49．9％。     

病理性近视眼的遗传流行病学研究

目的 对上海市眼耳鼻喉科医院病理性近视眼患者６２个家系的遗传方式进行研究,探讨可能的遗传模式。方法 用ＳＥＧＲＡＮＢ软件进行简单分离分析,计算确认概率π,并在此基础上计算分离比ｐ和散发概率ｘ,用ＳＡＧＥ－ＲＥＧＤ软件进行复合分离分析,探讨可能的遗传模式和致病基因概率。结果 婚配类型为Ｎ＊Ｎ的家系表现为常染色体隐性遗传,Ａ＊Ｎ婚配类型则可能为隐性遗传模式（不能排除显性遗传模式）,两种婚配类型中均在一     

农村地区自杀死亡与遗传因素的关系

目的:探讨农村自杀死亡与遗传因素的关系及不同特征一级亲属自杀遗传度的大小,为制定农村自杀的预防对策与措施提供依据.方法:在山东省疾病监测点上选取自杀死亡者153例,对照组153例,通过问卷调查获取他们的一级亲属资料,通过1∶1配对病例对照研究对他们及其一级亲属资料进行遗传流行病学研究,采用Penrose法估计遗传模式,Falconer回归法估算遗传度.结果:自杀家族史与自杀死亡高度相关(0R=13.25).一级亲属自杀遗传度(h2)为(34.0±6.4)％;≥60岁者的自杀遗传度为(51.2±7.0)％,＜60岁者(14.8±11.8)％;女性(23.2±10.2)％,男性(46.7±7.6)％;无精神障碍者(31.7±7.1)％,有精神障碍者(42.1±13.1)％;非暴力方式者(39.2±7.8)％,暴力方式者(25.4±10.7)％;低自杀意图者(21.6±13.6)％,高自杀意图者(38.1±7.1)％.结论:在农村自杀死亡者中,遗传因素可能是重要的危险因素,在较高年龄、男性、有精神障碍、非暴力方式、高自杀意图的自杀死亡者中遗传因素可能起更大的作用.     

非综合性唇腭裂的遗传学研究现状

先天性唇腭裂是人类最常见的先天性畸形之一，分为综合征性唇裂或唇腭裂、综合征性腭裂和非综合征性唇裂或唇腭裂、非综合征性腭裂，后是一种复杂的遗传性疾病，是一种基因遗传和环境因素相互作用所致的多基因多因素遗传疾病。确定遗传性疾病基因的首要工作是基因定位，国外主要通过候选基因法进行CL -P基因定位研究，在不同染色体区域筛选了几个可能易感基因位点，如2q13上的TGFα，6p23(0FCl)，17q21上的R肌气，4q254q31．3及19q13．2上的BCL3；CPO的遗传方式尚未得到证实，目前认为符合单一主基因隐性遗传模式，与一候选基因TGFA(位于2q13)相关；非综合征性唇腭裂完全不同于孟得尔式单基因遗传，属于数量性状遗传，具有显的遗传异质性，是一类极具挑战性和研究价值的遗传病，其基因定位和分析方法是现代遗传学的前沿和热点。     

汉族HLA-A等位基因与银屑病患者相关性研究

目的 探讨HLA-A等位基因与汉族人银屑病遗传易感性。方法 利用聚合酶链反应-序列特异性引物（PCR-SSP）法，对200例银屑病患者和204例健康人的HLA-A等位基因进行检测。结果 HLA-A*2601-05等位基因与汉族人银屑病呈正相关性（20.25%vs12.25%,RR=1.65,X^2=11.76,P=0.0006,Pc=0.0066),HLA-A*0201-17等位基因与汉族人银屑病呈负相关（4.25%vs9.80%,RR=0.43,X^2=10.26,P=0.0013,Pc=0.0143),HLA-A*2601-05等位基因仅与有家族史银屑病呈正相关（RR=2.04,X^2=12.49,P=0.0004,Pc=0.0044),HLA-A*2601-05等位基因与I型银屑病呈正相关（RR=1.68,X^2=11.67,P=0.0006,Pc=0.0066)。结论 HLA-A*2601-05可能是银屑病的易感基因或与易感基因相连锁。HLA-A*2601-05仅为有家族史银屑病和I型银屑病的危险基因。     

新疆维吾尔族寻常型银屑病中JAK1、STAT3蛋白的表达及意义

目的探讨JAK-STAT信号转导通路中JAK1和STAT3在新疆维吾尔族寻常型银屑病皮损组织中的表达及意义。方法采用免疫组化法检测45例维吾尔族寻常型银屑病皮损组织和21例维吾尔族正常表皮组织中JAK1和STAT3蛋白的表达,并复习相关文献。结果维吾尔族寻常型银屑病患者皮损组织中JAK1蛋白阳性率为77.78%,在维吾尔族正常表皮组织中的阳性率为28.57%;维吾尔族寻常型银屑病患者皮损组织中STAT3蛋白阳性率为86.67%,在维吾尔族正常表皮组织中的阳性率为23.81%,两组相比差异有统计学意义(P0.01)。结论维吾尔族寻常型银屑病发病可能与JAK-STAT信号转导通路中JAK1和STAT3蛋白异常表达相关。     

多囊卵巢综合征家系遗传方式研究

目的 探讨多囊卵巢综合征（polycystic ovary syndrome,PCOS)的遗传方式。方法 采用遗传流行病学中的简单分离分析和综合分离分析方法。对139PCOS患者一级亲属中女性月经不规律和男性早秃的发生情况进行分离比分析。结果 女性月经不规律在患者母亲和姐妹中的发生率分别为37．4％和33．1％,男性早秃在患者父亲和兄弟中的发生率分别为19．4％和6．5％,简单分离分析显示PCOS在子代的分离比为0．3023,综合分离分析显示其符合共显性完全外显有散发遗传模型,纯合致病基因频率为0．046。结论 PCOS呈共显性遗传方式。     

Diabetes mellitus: discrimination between single locus and muItifactorial models of inheritance

Family data from 6,559 diabetic propositi were analyzed using the method of complex segregation analysis in an attempt to discriminate the two models of two-allele single-locus inheritance and multifactorial inheritance for early, middle, and late onset diabetes. The three parameters in the single locus model were: degree of dominance, penetrance, and proportion of phenocopies. In early onset diabetes, the heritability estimated from the multifactorial model was so high as to inidcate major gene action. In middle and late onset diabetes, best fitting single-locus models were found to explain the data as well as the multifactorial model.     

Segregation Analysis of Prostate Cancer in France: Evidence for Autosomal Dominant Inheritance and Residual Brother-brother Dependence

Four segregation analyses concerning prostate cancer (CaP), three conducted in the United States and one in Northern Europe, have shown evidence for a dominant major gene but with different parameter estimates. A recent segregation analysis of Australian pedigrees has found a better fit of a two‐locus model than single‐locus models. This model included a dominantly inherited increased risk that was greater at younger ages and a recessively inherited or X‐linked increased risk that was greater at older ages. Recent linkage analyses have led to the detection of at least 8 CaP predisposing genes, suggesting a complex inheritance and genetic heterogeneity. To assess the nature of familial aggregation of prostate cancer in France, segregation analysis was conducted in 691 families ascertained through 691 CaP patients, recruited from three French hospitals and unselected with respect to age at diagnosis, clinical stage or family history. This mode of family inclusion, without any particular selection of the probands, is unique, as probands from all previous analyses were selected according to various criteria. Segregation analysis was carried out using the logistic hazard regressive model, as incorporated in the REGRESS program, which can accommodate a major gene effect, residual familial dependences of any origin (genetic and/or environmental), and covariates, while including survival analysis concepts. Segregation analysis showed evidence for the segregation of an autosomal dominant gene (allele frequency of 0.03%) with an additional brother‐brother dependence. The estimated cumulative risks of prostate cancer by age 85 years, among subjects with the at‐risk genotype, were 86% in the fathers' generation and 99% in the probands' generation. This study supports the model of Mendelian transmission of a rare autosomal dominant gene with high penetrance, and demonstrates that additional genetic and/or common sibling environmental factors are involved to account for the familial clustering of CaP.     

Genetics of club foot in Maori and Pacific people

The role of major gene and multifactorial inheritance in the aetiology of club foot in the New Zealand Polynesian population was studied using 287 New Zealand Maori and Pacific club foot families. The club foot family data were analysed by complex segregation analysis under the mixed model using the computer program POINTER. This analysis shows that the best genetic model for club foot in this population is a single dominant gene with a penetrance of 33% and a predicted gene frequency of 0.9%. These data provide a scientific foundation for molecular studies in the Maori and Polynesian population to identify putative club foot genes.


Keywords: club foot; New Zealand Maori; complex segregation analysis     

Evidence for the multigenic inheritance of schizophrenia.

Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy-seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome-wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the alpha 7-nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait-locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci.     

Family resemblance for fasting blood glucose in a population of Japanese Americans

The pattern of inheritance of fasting blood glucose was examined in a Japanese cohort of 500 nuclear families living in Hawaii. A principal component of glucose was defined to improve the ranking of diabetics and individuals receiving treatment (medication and/or diet) for hyperglycemia, thereby allowing as well as possible for inability to determine untreated levels in patients. Results from path and segregation analysis show that family resemblance for glucose is low in this population. The additive variation can be explained by a cultural model of inheritance without introducing intergenerational differences, a maternal-paternal effect, or even genetic parameters. Heritability is approximately 0.125. Complex segregation analysis provides no convincing evidence for a major gene, with preliminary support based upon leptokurtic outliers in five families disappearing on further analysis by partial truncation. A claim by other workers of a major recessive gene for hyperglycemia may be due to their failure to allow for treatment, skewness, and multifactorial heritability. In future, the search for major loci acting on liability to hyperglycemia should use multiple determinations of fasting glucose or be addressed to more primary and repeatable variables than fasting blood glucose.     

Major gene and multifactorial inheritance of mandibular prognathism

Mandibular prognathism typically shows familial aggregation. Various genetic models have been described and it is assumed to be a multifactorial and polygenic trait, with a threshold for expression. Our goal was to examine specific genetic models of the familial transmission of this trait. The study sample comprised of 2,562 individuals from 55 families. Complete family histories for each proband were ascertained and the affection status of relatives were confirmed by lateral cephalograms, photographs, and dental models. Pedigrees were drawn using PELICAN and complex segregation analysis was performed using POINTER. Parts of some pedigrees were excluded to create one founder pedigrees, so the total N was 2,050. Analysis showed more affected females than males (P = 0.030). The majority of the pedigrees suggest autosomal dominant inheritance. Incomplete penetrance was demonstrated by the ratio of affected/unaffected parents and siblings. The heritability of mandibular prognathism was estimated to be 0.316. We conclude that there is a major gene that influences the expression of mandibular prognathism with clear signs of Mendelian inheritance and a multifactorial component.     

Segregation analysis of microcephaly

Microcephaly is a heterogeneous disorder with genetic and environmental causes. However, there is little information on what proportion of cases are caused by inherited susceptibility, or the mode of inheritance in familial cases. To address these questions, we have performed classical and complex segregation analyses for microcephaly on 2 sets of family data collected from genetic counseling clinics in Vancouver and Jerusalem. These samples consisted of 143 affected individuals in 127 families ascertained from Vancouver, and 101 affected individuals in 59 families ascertained from Jerusalem. The results of the segregation analyses for the Vancouver sample indicated that approximately half of all microcephaly cases were due to highly penetrant recessive mutant alleles, with the remainder being sporadic. Although a recessive model allowing for the occurrence of sporadic cases fit the data from Vancouver best, a dominant model could not be statistically rejected. The classical segregation analysis on the Jerusalem sample suggested that both a dominant model with 29% of the cases being sporadic and a purely recessive model provided adequate fit to the data. Although the complex segregation analysis of this sample indicated that a dominant model provided a more parsimonious explanation for the observed familial variation, a recessive model was only marginally rejected. It should be noted that in the Jerusalem sample, families tended to be ascertained in the genetic counseling clinic only after the birth of a second affected child. This could be a potential bias which could inflate the segregation ratio, thus giving the impression of dominant inheritance. Our analyses, while confirming the complex nature of the cause of microcephaly, indicate that it may be necessary to await the results of genetic linkage analysis before a definitive mode of inheritance can be determined. © 1996 Wiley-Liss, Inc.     

Evidence for the multigenic inheritance of schizophrenia

Schizophrenia is assumed to have complex inheritance because of its high prevalence and sporadic familial transmission. Findings of linkage on different chromosomes in various studies corroborate this assumption. It is not known whether these findings represent heterogeneous inheritance, in which various ethnic groups inherit illness through different major gene effects, or multigenic inheritance, in which affected individuals inherit several common genetic abnormalities. This study therefore examined inheritance of schizophrenia at different genetic loci in a nationally collected European American and African American sample. Seventy‐seven families were previously genotyped at 458 markers for the NIMH Schizophrenia Genetics Initiative. Initial genetic analysis tested a dominant model, with schizophrenia and schizoaffective disorder, depressed type, as the affected phenotype. The families showed one genome‐wide significant linkage (Z = 3.97) at chromosome 15q14, which maps within 1 cM of a previous linkage at the α7‐nicotinic receptor gene. Chromosome 10p13 showed suggestive linkage (Z = 2.40). Six others (6q21, 9q32, 13q32, 15q24, 17p12, 20q13) were positive, with few differences between the two ethnic groups. The probability of each family transmitting schizophrenia through two genes is greater than expected from the combination of the independent segregation of each gene. Two trait‐locus linkage analysis supports a model in which genetic alleles associated with schizophrenia are relatively common in the general population and affected individuals inherit risk for illness through at least two different loci. © 2001 Wiley‐Liss, Inc.     

A Genetic Variant rs1020760at NFKB1 is Associated with Clinical Features of Psoriasis Vulgaris in a Han Chinese Population

Psoriasis vulgaris is a chronic inflammatory skin disease associated with complex genetic susceptibility. Recently, we identified a single‐nucleotide variant rs1020760 at NFKB1 significantly associated with psoriasis in a Han Chinese population in deep analysis of exome and targeted sequencing (P = 1.76 × 10^?8). To investigate the potential association between rs1020760 and phenotypes of psoriasis vulgaris, we performed a genotype–phenotype analysis. A total of 9946 cases and 9906 controls with detailed clinical and demographic information were involved in this study, while the genotype data of rs1020760 was available in the previous targeted sequencing study of psoriasis. Genotype‐based association testing revealed the additive model might provide the best fit for rs1020760 (P = 5.44 × 10^?8). Case‐only analysis showed that the distribution of allele G was significantly different between the cases with and without family history (P_allele = 4.07 × 10^?3,P_genotype = 5.75 × 10^?3). The differences in allele and genotype frequencies were observed between all the subphenotypes and controls except for the genotype frequency of the late onset subgroup, while no difference was found in case‐only analysis for the other two subphenotypes. Rs1020760 was preferentially associated with family history of psoriasis, implying that NFKB1 might not only play important roles in the development of psoriasis, but might also contribute to the special phenotypes of this disease.